The invention relates to “active implantable medical devices” as defined by Directive 90/385/EEC of 20 Jun. 1990 of the Council of the European Communities.
It is more specifically related to a neuromodulation microlead operating by multipoint stimulation of the central nervous system.
A neuromodulation lead is typically designed to be implanted in the cerebral venous network in order to target specific areas of the brain to apply electrical neurostimulation pulses for treating certain pathologies such as Parkinson's disease, epilepsy, etc. These techniques are grouped under the general term deep brain stimulation (DBS). The purpose of the lead may also be to stimulate the spinal cord, in particular for the treatment of pain. These techniques are known under the general name spinal cord stimulation (SCS).
These techniques differ in many aspects, including the methods used, from those employed in cardiology or in other types of nerve stimulation where the peripheral nervous system is stimulated, as in techniques known as vagus nerve stimulation (VNS) or analog techniques, where the electrodes are placed next to nerves or muscles, consequently in much more easily accessible areas.
The specificity of the leads for the stimulation of the central nervous system may results in the diameter of these leads being less than 1.5 French, or 0.5 mm, as well as having a lower number of electrodes to allow “multipoint” stimulation.
According to exemplary embodiments, the present disclosure provides a microlead structure that is able to reach deep brain areas in regions known as potentially effective in neuromodulation therapy, known under the name of the subthalamic nucleus (STN) or internal globus pallidus (GPI), and to precisely stimulate target areas located in these regions.
Current solutions of deep neurostimulation generally use a highly invasive approach, based on the perforation of the skull and on the implantation of the lead with an external guiding.
However, it would be desirable to provide methods enabling a far less invasive approach, through a venous access, implementing techniques similar to those used for the microcatheterization of the brain, used in the context of interventional neuroradiology. Provided that the leads have a sufficiently small diameter structure and are able to navigate in the venous and arterial system of the brain, these techniques could be used for the implantation of a microlead. In some implementations, the microlead must, however, remain suitable for permanent implantation in the brain.
Known microleads, however, face several major challenges using these methods.
First, leads of a too large diameter can cause severe neurological damage during the surgical implantation procedure. It is therefore necessary to greatly reduce the diameter of the microlead, while keeping its excellent maneuverability properties within the venous system to enable its implantation.
The cerebral arterial venous network includes high tortuosity and many branches, and it is essential to avoid trauma that a too rigid lead could provoke. But, conversely, too soft a microlead would be difficult to implant, due to a too low torsional stiffness to allow transmission of a rotation movement given from the proximal end over the entire length of the lead body until the distal end, (lack of “torquability”). Furthermore, a microlead that is too soft could not progress in the biological network without jamming under the effect of an axial thrust (lack of “pushability”).
Second, it is desirable that the implantable lead is compatible with the catheters of 1.6 French (0.53 mm) such as those already used today in interventional neuroradiology, for example for the delivery of devices such as springs (coils) during the treatment of intracranial aneurysms. This implies a lead having an overall diameter of less than 1.5 French (0.5 mm).
Third, the electrodes of a neurostimulation microlead should have an extremely small surface, so as to specifically stimulate targeted areas without the risk of producing serious psychiatric side effects, which unfortunately occurs today in a significant percentage of interventions.
Finally, it is desirable to have a very high number of neurostimulation electrodes on the same microlead, all being independently selectable, so as to refine the accuracy of the stimulated contact points. In some embodiments, the microlead may have at least 8 (e.g., from 20 to 100) independently programmable electrodes, with the possibility to select electrodes located in different angular directions on the same longitudinal position of the lead. This multiplication of the number of electrodes, and consequently of the independent conductors, may be implemented without detriment to the small diameter of the microlead, which reduces its traumaticity and offers access opportunities to deep brain areas.
Various neuromodulation lead structures with multiple conductors have been proposed, for example in WO 2007/115198 A2, US 2006/0111768 A1 or US 2010/0057176 A1, but for a relatively small number of conductors, and consequently the number of programmable electrodes (on the order of ten at most).
US 2006/0089697 A1 discloses a lead including a plurality of independent stranded conductors, distributed around a hollow tube, the assembly being protected by an outer insulation jacket. The tube is traversed through by a central lumen for permitting insertion of a delivery stylet which is inserted into this lumen during implantation. The overall diameter of this structure (at least 0.8 mm) is, however, much too high to achieve the deepest target areas of the brain.
US2013/0018445 A1 discloses a neurostimulation lead having up to 49 conductor strands spirally wound and individually insulated, but in an application for stimulation of a peripheral nerve located in a muscle or in adipose tissue, which is in an environment where the constraints of a very small diameter and of navigability are not met.
EP 2581107 A1 and EP 2719422 A1 (Sorin CRM) describe implantable microleads structures in venous, arterial or lymphatic networks. These microleads however are primarily designed for implantation into the coronary venous network for stimulation of the myocardium left ventricle, therefore in cardiology applications. Their structure is specifically designed to withstand very severe fatigue stresses related to the heartbeat, which cause material fatigue as a result of repeated bending from hundreds of millions of cycles, which can cause the lead to break and limit the lifespan.
These issues are much less critical in the case of a DBS or SCS neuromodulation microlead, which is implanted in a more static environment than the heart and is much less prone to fatigue stresses. Moreover, multiplying the number of independent electrodes (e.g., at least 8, such as from 20 to 100) cannot be satisfied by the microleads structures described in these documents, which may include at most seven independent conductors within a diameter of 1.5 French (0.5 mm).